Groups of diseases involving muscular disorder or myonecrosis are called myopathy. Muscular dystrophy and amyotrophy are representative examples of this class of disease. Muscular dystrophy is a collective term used for hereditary diseases that are characterized by gradual muscle weakening and atrophy. Progressive muscular dystrophies affect the largest number of patients, and cause hereditary, progressive muscle weakness. Amyotrophy is a neurogenic disease caused by damages in motor nerve.
The type of muscular dystrophy that affects the largest number of patients is Duchenne muscular dystrophy, which is a sex-linked recessive hereditary disease that develops only in males. The disease affects 3 to 5 individuals per 100,000 people, and 1 in 2,000 to 3,000 newborn males. The disease generally develops at the age of about 3 to 5 with defects in walking and standing, such as running problems and frequent falls. The ability to walk is lost by the age of around 10. These symptoms are followed by a rapid progress of spinal column deformation and arthrogryposis, which in many cases lead to respiratory failure, and, less often, heart failure and pneumonia.
The tests used for the diagnosis of muscular dystrophy include a blood test, a nerve conduction test, electromyography, a muscle biopsy, and a DNA analysis. The nerve conduction test finds whether mobility impairment or perception impairment stems from peripheral neuropathy, or looks for a damaged site or the extent of damage. The test measures the conduction rate of a stimulus in an electrostimulated nerve. By nature, the test requires special equipment, and, because an electrostimulation is directly applied to the nerve, the test is somewhat demanding in the sense that it involves shock, pain, and discomfort.
Electromyography finds whether mobility impairment originates in muscle or nerve, or looks for a damaged site or the extent of damage. The test requires special equipment, and involves pain from the insertion of a needle into the muscle. Pain-free, surface electromyography is available; however, the measurement must be performed at test facilities.
Muscle biopsy requires collecting a muscle tissue, and is therefore invasive and inconvenient. DNA analysis, necessary for the diagnosis of Duchenne and Becker muscular dystrophies caused by a mutation in the dystrophin gene, has not been applied to muscle degenerative diseases, and lacks versatility.
The blood test generally looks for creatine kinase. Creatine kinase is an enzyme predominantly present in the soluble fractions of skeletal muscle and cardiac muscle, and leaks into the blood from damaged cells. A damaged or dead skeletal muscle considerably raises the blood creatine kinase levels, and such high levels of blood creatine kinase can thus be used for the diagnosis of muscular dystrophy. However, because the blood creatine kinase levels can also increase in other diseases, a differential diagnosis solely based on creatine kinase concentration is difficult, and is made simultaneously with other tests.
The blood test that measures the blood creatine kinase is also performed for other progressive muscular dystrophies, and for diseases that involve muscle damage or death caused by nerve defects. However, as above, high blood creatine kinase levels also occur in diseases other than muscular disorders and myonecrosis, and other markers for muscular disorders and myonecrosis are needed.
Accordingly, there is a need for a method or a diagnosis kit that enables an early and easy diagnosis of muscle degenerative diseases such as muscular dystrophy.
11,15-Dioxo-9α-hydroxy-2,3,4,5-tetranorprostan-1,20-dioic acid (hereinafter, Tetranor-PGDM) is known as a metabolite of prostaglandin D2 (hereinafter, PGD2), and there is a report that the Tetranor-PGDM excreted into the urine increases through inflammation reactions in humans and mice, and that Tetranor-PGDM is a marker that reflects PGD2 production (Non-Patent Literature 1).
There are also reports that the increased expression of hematopoietic prostaglandin D synthetase (hereinafter, HPGDS) that catalyzes PGD2 production occurs at the affected sites of muscle degenerative diseases such as muscular dystrophy, and that PGD2 is involved in the prevention and improvement of disease progression (Patent Literature 1, Non-Patent Literature 2).
It is not known, however, that Tetranor-PGDM is detected in high concentrations as an excretion in the urine of patients with muscle degenerative diseases, and that the Tetranor-PGDM concentration significantly decreases by the administration of an HPGDS inhibitor.